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miR-29a-SIRT1-Wnt/β-Catenin Axis Regulates Tumor Progression and Survival in Hepatocellular Carcinoma

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Abstract

Sirtuin 1 (SIRT1) participates in the initiation and evolution of hepatocellular carcinoma (HCC). However, the specific mechanism of SIRT1 in HCC remains unclear. The mRNA expression of miR-29a in HCC were identified by qRT-PCR. miR-29a mimic and inhibitor were employed. The alteration of biological behavior was evaluated by Cell Counting Kit-8 (CCK8), clone formation, transwell and wound-healing assay. SIRT1 was verified to be a target gene which directly regulated by miR-29a. Luciferase reporter assay and co-IP were employed to evaluate the direct binding of miR-29a and SIRT1. Animal model was used to evaluate its function on tumor growth and metastasis in vivo. The relationship between miR-29a/SIRT1 and prognosis of HCC patients was analyzed. SIRT1 overexpression accompanied by low expression of miR-29a were detected in HCC which was negatively correlated, and associated with overall survival, vascular invasion and TNM stage. Up-regulation of miR-29a suppressed cell growth and motility. Deprivation of miR-29a expression led to opposite effect. The direct binding of miR-29a to SIRT1 was confirmed by luciferase reporter assay and co-IP. miR-29a repressed SIRT1, DKK2 and β-catenin, but their expression was obviously elevated by miR-29a inhibitor. Animal model suggested miR-29a could reduce the expression of SIRT1, thereby inhibiting HCC growth and metastasis by inactivating Wnt/β-catenin pathway. Low expression of miR-29a and high expression of SIRT1 predicted shorter survival time in HCC patients. miR-29a had the function of tumor suppressor which directly inhibited oncogenic SIRT1. The loss of miR-29a led to up-regulation of SIRT1, aggravate malignant transformation and poor prognosis of HCC.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

SIRT1:

Sirtuin 1

LC:

Liver cancer

HCC:

Hepatocellular carcinoma

miR-29:

MicroRNA-29

UTR:

Untranslated region

TACE:

Transcatheter arterial chemoembolization

NC:

Negative control

OE:

Overexpression

qRT-PCR:

Quantitative reverse transcription-polymerase chain reaction

CCK8:

Cell counting kit-8

OD:

Optical density

OS:

Overall survival

PBS:

Phosphatebuffered saline

IHC:

Immunohistochemistry

DAB:

Diaminobenzidine

HRP:

Horseradish peroxidase

SDS-PAGE:

Sodium dodecyl sulphate/polyacrylamide gel electrophoresis

SPF:

Specific pathogen-free

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Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China

    Liqiang Qian & Lei Qin

  2. Department of General Surgery, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, China

    Liqiang Qian, Gang Wang, Bin Li, Hemei Zhou & Jie Qiu

  3. School of Health and Social Care, Shanghai Urban Construction Vocational College, Shanghai, China

    Yanjun Zhang

Authors
  1. Liqiang Qian
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  2. Yanjun Zhang
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  3. Gang Wang
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  4. Bin Li
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  5. Hemei Zhou
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  6. Jie Qiu
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  7. Lei Qin
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Contributions

LQQ designed and analyzed the research study and wrote the manuscript; YJZ, GW, BL, HMZ and JQ collected and analyzed the data; LQ supervised the study, provided suggestive advice for the experiments, reviewed and edited manuscript.

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Correspondence to Lei Qin.

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The authors declare that they have no competing interests.

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Ethical Approval and Consent to Participate

The collection and use of clinical resources which performed in accordance with guidelines was complied with the permission of Biomedical Ethics Committee of Suzhou Ninth People’s Hospital (Approval number: KY2022-088-01, Suzhou, China). The written consent from each patient has been provided, which was conducted in accordance with the declaration of Helsinki. The procedures for animal models were approved by the Ethics Committee of Suzhou Ninth People’s Hospital (Approval number: KY2022-088-01, Suzhou, China), which was conducted in accordance with the declaration of Helsinki.

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Qian, L., Zhang, Y., Wang, G. et al. miR-29a-SIRT1-Wnt/β-Catenin Axis Regulates Tumor Progression and Survival in Hepatocellular Carcinoma. Biochem Genet (2023). https://doi.org/10.1007/s10528-023-10521-7

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  • DOI: https://doi.org/10.1007/s10528-023-10521-7

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